The discovery of a theoretical method for the prediction of cyclo-addition reaction products, and the resulting possibilities for the design of syntheses of new hterocyclic systems which are close analogs to clinical antitumor drugs, antihypertensives, tranquilizers, and antiallergenic drugs, prompted this research program. The main objective of this project is to synthesize new drugs for cancer, hypertension, psychosis, and allergy chemo-therapy. A secondary objective is to apply molecular orbital theory to drug design, based on the principle that a theoretical method of predicting chemical reactivities will also be useful in predicting in vivo pharmacological activity. The reactions to be studied both experimentally and spectroscopically include those between dienes or 1,3-dipoles and fulvenes, dienes, or 1,3-dipoles with tropones and related trienes, tetrazines with dienes and trienes, and of phosphorus, sulfur, and nitrogen substituted alkenes with 1,3-dipoles. BIBLIOGRAPHIC REFERENCES: K. N. Houk, "The Frontier Molecular Orbital Theory of Cycloaddition Reaction", Accounts of Chemical Research, approximately 8, 36l (1975).K. N. Houk and L. L. Manchausen, "Ionization Potentials, Electron Affinities, and Reactivities of Cyanoalkenes and Related Electron-Deficient Alkenes. A Frontier Molecular Orbital Treatment of Cuanoalkene Reactivities in Cycloaddition, Electrophilic, Nucleophilic and Radical Reactions", accepted for publiation, J. Amer. Chem. Soc., approximately 98,000 (l975).